Jaewoong Lee, PhD
Cards
About
Research
Publications
2024
Leveraging altered lipid metabolism in treating B cell malignancies
Lee J, Mani A, Shin M, Krauss R. Leveraging altered lipid metabolism in treating B cell malignancies. Progress In Lipid Research 2024, 95: 101288. PMID: 38964473, DOI: 10.1016/j.plipres.2024.101288.Peer-Reviewed Original ResearchB-cell malignanciesMalignant B cellsB cell receptorAltered lipid metabolismLipid metabolismOncogenic signalingB cellsTreating B-cell malignanciesReprogram lipid metabolismLipid raft integrityB-cell receptor activationHeterogeneous blood cancerImprove risk stratificationUncontrolled cell proliferationB cell activationRaft integrityLipid raftsMYC translocationCytotoxic therapyHeightened metabolic demandsGenetic driversSignaling cascadesMalignant subtypeRisk stratificationObese individuals
2023
Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies
Kume K, Lee J, Cheng Z, Robinson M, Leveille E, Cosgun K, Chan L, Feng Y, Arce D, Khanduja D, Toomre D, Müschen M. Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 4138. DOI: 10.1182/blood-2023-190926.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lymphomaMature B-cell lymphomasB cell deathB cellsB cell developmentGenetic deletionMantle cell lymphomaNF-kB signalingBCR signal inhibitorsB cell precursorsCell of originCell viabilityChronic active BCRB cell survivalB cell receptor signalsHodgkin's diseaseMultiple myelomaNormal B cell developmentPlasma cellsBtk tyrosine kinaseCell lymphomaBurkitt's lymphomaNF-kBSmall molecule inhibitorsRepurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathwayDynamic Recruitment of Inhibitory Complexes Controls Oncogenic Signaling in B-Cell Malignancies
Sun R, Lee J, Robinson M, Kume K, Ma N, Cosgun K, Chan L, Antoshkina I, Khanduja D, Leveille E, Katz S, Chen J, Paietta E, Vaidehi N, Müschen M. Dynamic Recruitment of Inhibitory Complexes Controls Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 719. DOI: 10.1182/blood-2023-189742.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lymphomaHigher serum levelsMature B-cell lymphomasSoluble CD25Serum levelsOncogenic signalingMouse modelB cellsAggressive B-cell lymphomasAcceleration of diseaseActivation of inhibitoryPoor clinical outcomeCD25 surface expressionB cell subsetsRole of CD25Patient-derived xenograftsB cell populationsB-cell receptor signalingB-cell leukemiaGenetic mouse modelsKnockin mouse modelCell deathMature B cell populationClinical outcomes
2021
PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis
Pan L, Hong C, Chan LN, Xiao G, Malvi P, Robinson ME, Geng H, Reddy ST, Lee J, Khairnar V, Cosgun KN, Xu L, Kume K, Sadras T, Wang S, Wajapeyee N, Müschen M. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016553118. PMID: 33531346, PMCID: PMC7896313, DOI: 10.1073/pnas.2016553118.Peer-Reviewed Original ResearchConceptsTransplant recipient miceDNA double-strand breaksNormal B cell developmentDouble-strand breaksB cell developmentGenetic deletionB cellsLymphoid transcription factorsGlucose transporter GLUT1Gatekeeper functionGlucose uptakeRecipient miceTranscription factorsSomatic recombinationSynthetic lethalityB-cell acute lymphoblastic leukemiaCell developmentMetabolic gatekeeperRefractory B-ALLDeficient murineCell acute lymphoblastic leukemiaPoor clinical outcomeCell typesAcute lymphoblastic leukemiaGlucose transport
2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3Signalling input from divergent pathways subverts B cell transformation
Chan LN, Murakami MA, Robinson ME, Caeser R, Sadras T, Lee J, Cosgun KN, Kume K, Khairnar V, Xiao G, Ahmed MA, Aghania E, Deb G, Hurtz C, Shojaee S, Hong C, Pölönen P, Nix MA, Chen Z, Chen CW, Chen J, Vogt A, Heinäniemi M, Lohi O, Wiita AP, Izraeli S, Geng H, Weinstock DM, Müschen M. Signalling input from divergent pathways subverts B cell transformation. Nature 2020, 583: 845-851. PMID: 32699415, PMCID: PMC7394729, DOI: 10.1038/s41586-020-2513-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell Line, TumorCell Transformation, NeoplasticEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansLeukemia, B-CellMiceProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycSignal TransductionSTAT5 Transcription FactorConceptsPre-B cell receptorPrincipal oncogenic driverDivergent pathwaysSignal transduction proteinsPro-B cell stageSingle-cell mutationTranscription factor MYCOncogenic driversDivergent signaling pathwaysSingle oncogenic pathwayCentral oncogenic driverMore mature cellsGenetic reactivationTranscriptional programsB-cell transformationProtein kinasePathway componentsERK activationIndividual mutationsOncogenic STAT5Signaling pathwaysCell transformationCytokine receptorsGenetic lesionsDivergent circuits
2018
Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells
Sullivan-Reed K, Bolton-Gillespie E, Dasgupta Y, Langer S, Siciliano M, Nieborowska-Skorska M, Hanamshet K, Belyaeva EA, Bernhardy AJ, Lee J, Moore M, Zhao H, Valent P, Matlawska-Wasowska K, Müschen M, Bhatia S, Bhatia R, Johnson N, Wasik MA, Mazin AV, Skorski T. Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells. Cell Reports 2018, 23: 3127-3136. PMID: 29898385, PMCID: PMC6082171, DOI: 10.1016/j.celrep.2018.05.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinDNA RepairFemaleFusion Proteins, bcr-ablHomologous RecombinationHumansImatinib MesylateKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMiceMice, Inbred NODMice, KnockoutPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Rad52 DNA Repair and Recombination ProteinSynthetic Lethal MutationsTumor Suppressor p53-Binding Protein 1ConceptsTumor cellsBRCA-deficient tumor cellsSimultaneous targetingBRCA-deficient tumorsClinical trialsProlonged latencyImmunodeficient miceTherapeutic outcomesBRCA1-deficient tumorsPARP inhibitorsBRCA-deficient cellsMinimal toxicitySynergistic activitySynthetic lethal effectTumorsNormal cellsPARPiSynthetic lethalityInhibitorsLethal effectsCellsDominant negative mutantSynergistic accumulationMalignancyTargetingB-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies
Xiao G, Chan LN, Klemm L, Braas D, Chen Z, Geng H, Zhang QC, Aghajanirefah A, Cosgun KN, Sadras T, Lee J, Mirzapoiazova T, Salgia R, Ernst T, Hochhaus A, Jumaa H, Jiang X, Weinstock DM, Graeber TG, Müschen M. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies. Cell 2018, 173: 470-484.e18. PMID: 29551267, PMCID: PMC6284818, DOI: 10.1016/j.cell.2018.02.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCarbonCell Line, TumorCell SurvivalGlucoseGlucosephosphate DehydrogenaseGlycolysisHumansIkaros Transcription FactorMiceMice, Inbred C57BLMice, Inbred NODOxidative StressPAX5 Transcription FactorPentose Phosphate PathwayPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Phosphatase 2Proto-Oncogene Proteins c-bcl-2Transcription, GeneticConceptsPentose phosphate pathwayCarbon utilizationSerine/threonine protein phosphatase 2AB-cell transcription factor PAX5Transcription factor Pax5Favor of glycolysisSmall molecule inhibitionPhosphatase 2ATranscriptional repressionRedox homeostasisOncogenic transformationTumor suppressorMolecule inhibitionPP2AGenetic studiesPhosphate pathwayB cell activationEssential roleB-cell malignanciesCell malignanciesB cellsAntioxidant protectionOxidative stressB-cell tumorsCell activation
2017
Metabolic gatekeeper function of B-lymphoid transcription factors
Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature 2017, 542: 479-483. PMID: 28192788, PMCID: PMC5621518, DOI: 10.1038/nature21076.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsB-LymphocytesCarcinogenesisCarrier ProteinsCell DeathChromatin ImmunoprecipitationCitric Acid CycleDisease Models, AnimalEnergy MetabolismFemaleGene Expression Regulation, NeoplasticGlucocorticoidsGlucoseHumansIkaros Transcription FactorMiceMice, TransgenicPAX5 Transcription FactorPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Serine-Threonine KinasesPyruvic AcidReceptor, Cannabinoid, CB2Receptors, GlucocorticoidSequence Analysis, RNATranscription Factors